Short oligodeoxynucleotides, incorporating nucleotides modified by the addition of reactive crosslinking arms, be synthesized. These oligonucleotides should hybridize with target sequences in mRNA or DNA, and once bound, should covalently crosslink with the complementary sequence via the incorporated modified nucleotide. In particular, derivatives of 4-aminopyrazolo(3, 4-d) pyrimidine, with a haloalkyl or similar substituent in the 3- position, will be prepared. These derivatives are isosteric with a 7-substituted purine and should be capable of crosslinking with the 7-position of a purine in an adjacent base pair of the complementary strand. This modified nucleoside will be converted into a blocked phosphoramidite and incorporated into an oligonucleotide on a DNA synthesizer. This olignucleotide will be tested for covalent crosslinking to complementary and non- complementary DNA restriction fragments. Such antisense crosslinkable oligonucleotides, designed to minimize host toxicity, may be useful as chemotherapeutic agents for infectious diseases and cancer. They will be targeted at the mRNA or DNA of microorganisms or of any cancer tissue in which a rearranged oncogene is expessed.